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Spectrochimica Acta Part A 72 (2009) 1097–1102

Contents lists available at ScienceDirect

Spectrochimica Acta Part A: Molecular andBiomolecular Spectroscopy

journa l homepage: www.e lsev ier .com/ locate /saa

ole of hydrogen bonding on the spectroscopic properties of thiazolidinedioneerivatives in homogeneous solvents

rindam Sarkara, Paltu Banerjeea, Sk. Ugir Hossainb, Sudin Bhattacharyab,ubhash Chandra Bhattacharyaa,∗

Department of Chemistry, Jadavpur University, Kolkata 700032, IndiaDepartment of Cancer Chemoprevention, Chittaranjan National Cancer Institute, 37, S.P. Mukherjee Road, Kolkata 700026, India

r t i c l e i n f o

rticle history:eceived 6 November 2008

a b s t r a c t

In this work, three newly synthesized derivatives of thiazolidinediones, with potential for application asdrugs in pharmaceutical industry and free radical scavenging activity, have been taken up to investigate

eceived in revised form 15 December 2008ccepted 3 January 2009

eywords:xcited state propertyecay constantubstituent effect

their behaviour in different homogeneous solvents. The purpose of this work is to study the solvationcharacteristics in ground and excited states of the derivatives by monitoring the absorbance and fluo-rescence band maxima. The steady state and time resolved fluorescence studies in protic and aproticsolvents have been rationalized on the basis of solute–solvent interaction and substituent effect on thesephotophysical processes have been analyzed. Substituents at different positions of the aryl moiety affectthe hydrogen bond formation ability of the probes.

olvent polarity

. Introduction

Thiazolidinedione derivatives (TZD) have been found to possessotent immunostimulatory property, antiarthritic, antidiabetic asell as oncostatic activities [1] and are reducer of plasma glucose

evel in vivo [2]. These compounds suppress the growth of severalancer cell lines including colon, breast and prostate [3–9]. Theyre found to inhibit angiogenesis and are also potential chemo-reventive agents against tongue and gastric carcinogenesis [10].hese compounds have free radical scavenging property. Free rad-cals are formed during normal cellular metabolism. Exposuref a healthy cell to free radical is known to damage structuresnd consequently interfere with functions of enzymes and criticalacromolecules. A balance between the formation of free radicals

nd their detoxification is essential for normal cellular function.hen such a balance is disrupted due to excessive generation of free

adicals or low level of antioxidants, a cell enters a state of oxidative

tress and is damaged. TZD’s are used to destroy these free radicalsy scavenging them [10,11]. Interest in the photophysical studies ofhese probes in homogeneous solvents originates mainly from twospects: the first one arises from their potential for novel biological

∗ Corresponding author at: Department of Chemistry, Jadavpur University, Raja.C. Mallick Road, Kolkata 700032, West Bengal, India. Tel.: +91 33 2414 6223;ax: +91 3324146584.

E-mail addresses: sbjuchem@yahoo.com, scbhattacharyya@chemistry.jdvu.ac.inS.C. Bhattacharya).

386-1425/$ – see front matter © 2009 Elsevier B.V. All rights reserved.oi:10.1016/j.saa.2009.01.001

© 2009 Elsevier B.V. All rights reserved.

applications in pharmaceuticals and the second one arises due totheir free radical scavenging activity. These fluorescent probes indi-cate intrinsically wide applications in pharmaceutical industries.Since these TZD derivatives are newly synthesized, their photo-physical study is rare in literature. The optical response of a solutein a solvent reflects the solute–solvent interactions on a micro-scopic level and thus the spectral parameters, e.g. the transitionenergy, fluorescence quantum yield and other photophysical prop-erties are dependent on the nature of the molecular environmentaround the solute. In this work three newly synthesized deriva-tives of thiazolidinediones have been taken up to investigate theirphotophysical behaviour in different solvents using spectroscopictechnique.

Hydrogen bonding and solvent polarity are the key factors incontrolling pathways of energy dissipation following electronicexcitation [12,13]. Solvent-moderated shifts of the energy levelsmay enhance or inhibit radiationless transitions to the ground statevia the “proximity effect” discussed by Lim [14]. Hydrogen bondformation has a different effect on the energies of various excitedstates; in an extreme case, hydrogen bonding may cause the rever-sal of close-lying n, �* and �, �* states [15]. In addition, differencein strength of hydrogen bonding in the ground and excited statesmay lead to efficient energy dissipation [16–20].

The dependence of the photophysical properties of the probeson solvent polarity is clearly indicated by the large hypsochromicshift in fluorescence observed from polar to non-polar solvents. Theresults have been analyzed considering solute–solvent interactionsto different extent.

1 a Acta Part A 72 (2009) 1097–1102

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098 A. Sarkar et al. / Spectrochimic

. Structures

. Synthesis scheme

. Experimental details

The thiazolidinedione derivatives were synthesized followinghe procedure mentioned in the synthesis scheme [10]. Theseere recrystallized before use. All the solvents used, were of AR

rade. The purified solvents were found to be free from impuri-ies and were transparent in the spectral region of interest. Thehotophysics of the thiazolidinedione (TZD: A, B, C) probes in var-

ous solvents were studied applying absorbance, fluorescence andifetime measurement techniques. Absorption spectra of the TZDrobes were recorded using a Pharmaspec UV–vis 1700 spectropho-ometer (Shimadzu), with a matched pair of silica cuvettes (pathength 1 cm). The emission spectra of the probes were recordedsing spectrofluorimeter (Fluorolog FII A Spectrofluorimeter, Spex

nc., NJ, USA) with a slit width of 1.25 mm. Fluorescence life-ime measurements were performed using time correlated singlehoton counting method and using a nanosecond diode laser at70 nm (IBH, nanoLED-7) as light source. The response time of thenstrument is 1.1 ns. The decays were analyzed using IBH DAS-6ecay analysis software. Geometrical optimization and ground stateipole moment calculations were performed using semiempiricalolecular orbital methods at the Austin model 1 (AM 1) level usingOPAC programme. The fluorescence quantum yields (ϕf) of TZD, B and C were measured using fluorscein (ϕf = 0.9 in 0.01N NaOH)s the reference compound [21].

. Structural behaviour of the TZD’s

In the electronic excited state, many molecules have dipoleoments larger than in the ground state [22]. The dynamic changes

f the dipole sometimes induce formation of a strong hydrogenond in the excited state [23]. Amongst the three TZD derivatives, B, and C, hydrogen bond forming ability of the probes with theolvent should decrease in the order A > B > C, since compound Aill be more solvated compared to B and C due to the presence of

ulky –OMe groups around –OH group in the aryl moiety of B and

C. A gradual change in solvent polarity from polar to non-polar alsoreduces the strength and probability of hydrogen bond formation.The NH group and carbonyl groups present in the thiazolidinedionemoiety are also potential hydrogen bond forming sites. The inter-action at the NH site depends on the electron density on that sitewhich is in turn governed by the substituents present in the arylmoiety. Due to the presence of keto groups on both sides of thethiazolidinedione moiety, a positively charged center is formed atthe nitrogen, thus making it electron deficient. So it will act as thepotential electron-accepting site when mixed with some electrondonating solvents like DMF.

6. Results and discussion

6.1. Absorbance and fluorescence

The UV–vis absorption spectra of the compounds A, B and Cwere studied in various solvents of different polarity and the spec-tral data have been collected in Table 1. The absorbance maximaof the probes were observed to shift in solvents of different polar-ity (Fig. 1). The absorption of the compound, characterized by abroad band, corresponds to � → �* transition of the molecule to S1.The absorption is intense and the peak position is sensitive to thepolarity of the medium. The magnitude of the shifts suggests thatthe ground state of the molecule is polar.

The fluorescence spectra of the compounds are shown in Fig. 2.The wavelengths corresponding to the fluorescence maxima arecollected in Table 1. An increase in the polarity of the medium leadsto a bathochromic shift in the fluorescence maxima. The effect ofthe polarity of the medium on the fluorescence maximum is morepronounced than that on the absorption maximum. The magni-

tude of the spectral shift in absorption is 4 nm, 7 nm and 4 nm forcompounds A, B and C, respectively for changing the solvent fromcyclohexane to water, whereas this shift in fluorescence maxima is83 nm, 74 nm, and 89 nm for compounds A, B and C, respectively.The magnitude of the shift in wavelength of fluorescence maxima

A. Sarkar et al. / Spectrochimica Acta Part A 72 (2009) 1097–1102 1099

Table 1Absorption and emission characteristics of the probes in various solvents.

Solvent TZD �absmax/nm �fls

max/nm ET(30)/kcal mol−1

Cyclohexane A 347 39731.2B 348 400

C 354 408

Dioxan A 350 41836.3B 358 420

C 367 430

DMF A 353 42443.9B 340 417

C 341 408ACN A 348 428

46B 354 430C 362 450

Methanol A 352 42855.5B 355 424

C 359 437

Ethylene glycol A 360 44056.3B 361 435

C 370 466

Glycerol A 364 45157B 367 447

C 364 457

W

imgtarw[tmspplia

Fa

ater A 351 48063.1B 355 474

C 358 497

s approximately 21, 10.5 and 22 times as large as in the absorptionaxima. The excited state properties differ much from those in the

round state. The shift in the fluorescence maxima over absorp-ion maxima suggests that the emitting states of the compoundsre more polar than the ground state. The transition energy cor-esponding to the absorption maxima E(A) is linearly correlatedith the transition energy for intramolecular charge transfer band

ET(30)] [24,25] values of the solvents (fig not shown). Like absorp-ion energy, the transition energy corresponding to the fluorescence

axima E(F) is also linearly correlated with ET(30) values of theolvents. A plot of Stokes shift vs. ET(30) of the solvents was alsolotted (Fig. 3). The data points formed two separate classes. For

rotic solvents, a line with higher slope and for aprotic solvents, a

ine with a lower slope was obtained. This difference in behaviourndicates the importance of hydrogen bonding in the ground states well as in the excited state. The large blue shift on the fluores-

ig. 1. Absorption spectra of TZD C in (1) water, (2) methanol, (3) dioxan, (4) ACNnd (5) ethylene glycol. [C] = 18.7 × 10−6 M.

Fig. 2. Fluorescence spectra of A in (1) water, (2) methanol, (3) ACN, (4) cyclohex-ane, (5) dioxan, (6) DMF. Inset: fluorescence spectra of B in (1) water, (2) ACN, (3)MeOH, (4) cyclohexane, (5) dioxan, (6) ethylene glycol, (7) DMF. [A] = 17.2 × 10−6 M,[B] = 17.8 × 10−6 M.

cence spectra on changing the solvent from water to cyclohexaneindicates the effect of hydrogen bonding in the excited state of theprobes. The probes exhibited enhanced fluorescence intensity onchanging the solvent from water to cyclohexane with appreciableblue shift. The low fluorescence intensities of the probes in polarsolvents like water are likely due to the radiationless decay of theprobes, due to hydrogen bonding. The influence of the phenyl moi-ety with substitution at different positions of the probes could beassessed from the spectral data presented in Table 1. Substitutionof –OMe group and OH group at 3 and 4 position in B while –OMegroups at 3 and 5 positions and −OH group at 4 position in C makethe compounds behave differently from A which has only one −OHgroup at 2 position of the benzene ring.

6.2. Multiple linear regression analysis

In order to obtain an insight into the various modes of solvation

determining the absorption and fluorescence energies, the multi-ple linear regression analysis approach of Abraham et al. [26] hasbeen used. Correlation of E(A) and E(F) were found with Taft’s �*

value, an index of the solvent dipolarity/polarizability and the ˛

Fig. 3. Plot of Stokes shift vs. ET(30) of different solvents for A.

1 a Acta

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E

E

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100 A. Sarkar et al. / Spectrochimic

nd ˇ [27] values representing the hydrogen bond donating andccepting ability, respectively of the solvent. The following regres-ion equations were obtained for A, B and C, respectively

For A:

(A) = 82.32 − 0.71˛ − 2.07ˇ − 0.27�∗

(F) = 71.52 − 2.58˛ + 5.03ˇ − 8.78�∗

For B:

(A) = 80.86 − 1.72˛ + 1.13ˇ + 0.19�∗

(F) = 70.79 − 2.45˛ + 6.35ˇ − 8.03�∗

For C:

(A) = 78.87 − 1.74˛ + 1.82ˇ + 0.89�∗

(F) = 68.82 − 4.57˛ + 8.86ˇ − 7.99�∗

For E(A), the ratio of the regression coefficients of ˇ and ˛ indi-ates the relative importance of hydrogen bond acceptance overonation by the solvents with the compounds. The ratio is 3 for A,.65 for B and 1.04 for C, indicating that B and C behave differentlyrom A due to the –OMe substituent present in them. From the E(F)alues, it is observed that the solvent dipolar interaction (�*) andydrogen bond accepting property (ˇ), play a greater role. The ratio

ndicating the relative importance of �* over ˇ is 1.74 for A, 1.26 forand 0.90 for C. This indicates that dipolar interactions predomi-

ate in the excited state properties of A and B but hydrogen bondormation property predominates in C. The intercept values indi-ate the E(F) and E(A) values of the probes in a purely non-polarolvent like cyclohexane, where there is no specific interaction. Thebserved E(F) and E(A) values of the three probes in cyclohexanere very close to the intercept values, which have been theoreticallyalculated by using the multiple linear regression analysis.

.3. Dipole moment calculation

The dipole moments of the compounds were determined by theolvatochromic comparison method, using the equations [28]:

(A) + E(F) = (�20 − �2

1)[2(ε − 1)]

a3(2ε + 1)+ 2�G(gas) + �(sp)

nd

(A) − E(F) =[

(�1 − �0)2

a3

][2(ε − 1)(2ε + 1)

− 2(n2 − 1)(2n2 + 1)

]

here, ε and n are the dielectric constants and refractive indicesf the solvents, respectively. �G (gas) is the value of �G in theas phase and ‘a’ is the Onsager cavity radius of the probes. Thesequations are valid for aprotic solvents where specific interactions

able 2hange in free energy of solvation (�Gsolvation) and reorganization energies (�) of the prob

olvent Probes

TZD A TZD B

�G/kcal mol−1 �/kcal mol−1 �G/kcal m

yclohexane 76.90 5.17 76.51ioxan 74.75 6.62 73.67MF 73.92 6.75 76.02CN 74.03 7.80 73.29ethanol 73.27 7.18 73.69

G 71.91 7.19 72.18lycerol 70.69 7.55 70.65ater 70.27 10.87 70.06

Part A 72 (2009) 1097–1102

(�sp) are absent. [E(A) + E(F)] and [E(A) − E(F)] were plotted againstappropriate dielectric functions and the ratio of the dipole momentin the S1 state (�1) to that in S0 state (�0) was obtained fromthe ratio of the slopes from the two plots. From semiempiricalmolecular orbital calculations at the Austin model 1 (AM 1) levelusing MOPAC programme involving complete geometry optimiza-tion of the ground state of the compounds, the ground state dipolemoments (�0) obtained are 2.72 D, 5.30 D and 0.82 D for A, B and C,respectively. Using the �0 values from AM 1 calculation; the (�1)values obtained from the slope ratio are 4.48 D, 7.72 D and 0.87 Dfor A, B and C, respectively. The ratio of decreased dipole momentfrom ground to excited state for the three compounds are in theorder A > B > C which is in accordance to their structural symmetry.The (�1/�0) value is 1.64 for A, 1.45 for B and 1.06 for C. It will thusfacilitate greater extent of dipolar interactions between the probesand the solvents in the excited state. This is also explained by theE(F) value in ACN, where dipole–dipole interactions play the mainrole in A and B whereas in C, the interaction is less.

6.4. Free energy change of solvation and reorganisation energies

The free energy change of solvation and reorganization energiesof the probes in various solvents have been calculated (Table 2).According to Marcus [29–32] one can partition E(A) and E(F) asfollows:

E(A) = �G(solv) + �1

E(F) = �G(solv) − �0

where �G (solv) is the difference in free energy of the ground stateand the equilibrium excited state in a given solvent and � representsthe reorganization energy. Under the condition that �0 ≈ �1 ≈ �, weget

E(A) + E(F) = 2�G(solv) and E(A) − E(F) = 2�

The �G (solv) values for the probes are maximum for cyclo-hexane since it is purely nonpolar and also the ˛ and ˇ valuesof cycohexane are zero. The �G (solv) values are minimum inwater. The difference between these values (water and cyclohex-ane) should give the free energy change required for hydrogen bondformation. The plot of � (�G) (solv), i.e. (�Gcyclohexane − �Gwater)vs. ET(30) has been depicted in Fig. 4. These values of the com-pounds in other hydrogen bond forming solvents like methanol,ethylene glycol, glycerol and dioxan is of the order of the hydro-gen bond energy [33]. In the aprotic solvents the values are small

and interaction of the probes with those solvents is purely out ofdipolar interactions in the excited state. The reorganization energyvalues of the probes in different solvents also follow this trend. The� value is small and minimum in cyclohexane. It has a higher valuein water, which is expected.

es in various solvents.

TZD C

ol−1 �/kcal mol−1 �G/kcal mol−1 �/kcal mol−1

5.31 74.90 5.125.87 71.91 5.687.73 76.65 6.856.75 70.97 7.696.52 72.28 7.116.71 69.04 7.936.94 70.28 7.9610.16 68.42 11.12

A. Sarkar et al. / Spectrochimica Acta Part A 72 (2009) 1097–1102 1101

6

sliyght(c

6

i

TS

S

C

D

D

A

M

E

G

W

Fig. 4. Plot of � (�G) vs. ET(30) of different solvents for A.

.5. Fluorescence quantum yield

Fluorescence quantum yield (ϕf) of the probes A, B and C are sen-itive towards solvent polarity. In aqueous solution of the probesow quantum yield is obtained. The values increased on chang-ng the solvent from polar to a non-polar one. The low quantumield values in polar solvents are due to the formation of hydro-en bond between the probes and the solvent. The exceptionallyigh quantum yield values in ethylene glycol and glycerol are dueo the increased viscosity of the medium. The quantum yield valuesTable 3) were used to calculate the radiative and non-radiative rateonstants of the probes in different solvents.

.6. Time resolved fluorescence decay

The fluorescence decay behaviour of the systems has been stud-ed in solvents of varying polarity. In all the cases for the compounds

able 3pectroscopic parameters of the probes in various solvents.

olvent Compound ( kr × 10−7/s−1 knr × 10−9/s−1

yclohexaneA 0.020 2.17 1.06B 0.018 2.95 1.60C 0.032 3.40 1.03

ioxanA 0.031 1.86 0.58B 0.017 1.31 0.76C 0.030 2.09 0.67

MFA 0.064 2.03 0.29B 0.023 0.56 0.24C 0.042 0.94 0.21

CNA 0.025 6.94 2.86B 0.010 3.44 3.95C 0.020 3.84 1.88

ethanolA 0.020 5.88 2.88B 0.012 4.80 3.95C 0.034 8.71 2.47

thylene glycolA 0.115 3.12 0.24B 0.104 4.12 0.35C 0.108 4.80 0.40

lycerolA 0.632 9.87 0.05B 0.350 6.04 0.11C 0.380 7.72 0.13

aterA 0.011 1.71 1.54B 0.011 3.92 3.53C 0.027 7.94 2.86

Fig. 5. Fluorescence decay curve of A in water and DMF. [A] = 17.2 × 10−6 M.

A, B and C, biexponential fitting was observed irrespective of the sol-vent polarity. The biexponential fitting does not necessarily indicatethat the decay curves have only two discrete time constants; it maybe caused by the probes experiencing two different local confor-mations resulting from the hydrogen bonding interaction betweenthe probes and the solvents. The lifetime values were calculatedusing the expression, I(t) = ∑n

i=1Aie−t/� i where, I(t) is the intensity

of the fluorescence at time t, Ai is the pre-exponential factor forthe fraction of the fluorescence intensity, �i is the fluorescence life-time of the emitting species and n is the total number of emittingspecies. The average fluorescence lifetimes were calculated usingthe relation �avg = (a1�1 + a2�2)/(a1 + a2), where a1 and a2 are pre-exponential factors. Typical decay profiles are shown in Fig. 5. Thethree probes have a higher fluorescence decay time in aprotic sol-vents, whereas in protic solvents, the decay time is lower due tohydrogen bonding interaction. In case of ethylene glycol and glyc-erol, the decay time is higher which is due to the increased viscosityof the media. The effect of polarity on decay time is very similarto that observed for fluorescence quantum yield. Increase in thepolarity of the solvent leads to a shortening of lifetime. However,in DMF the probes show a higher lifetime value, which may bedue to an enhanced stability as a result of electron transfer fromthe electron-rich DMF to the electron deficient –NH center of theprobes.

6.7. Radiative and nonradiative rate constants

The radiative (kr) and non-radiative (knr) rate constants of thesystems in different solvents have been determined using the fol-lowing relations and the values are given in Table 3.

kr = ϕf

�fand knr = (1 − ϕf)

�f

where ϕf and �f are the quantum yield and average lifetime valuesof the probes, respectively.

The radiative rate constants of the probes depend on the substi-tution of –OCH3 group in the moiety. In protic and aprotic solventsthe knr values are 102 times higher than the kr values. To investigatethe role of specific and non-specific solute–solvent interactions andsubstitution effect on the decay constants, a plot of log (knr/kr) vs.

ET(30) was plotted for the three derivatives (Fig. 6). It is observedthat with increase in the ET(30) values of the solvents, log (knr/kr)values of the probes increased gradually. Thus, with increase in sol-vent polarity, the probes are gradually getting involved in hydrogenbond formation with the solvents. This indicates that the hydrogen

1102 A. Sarkar et al. / Spectrochimica Acta

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[[29] R.A. Marcus, J. Chem. Phys. 38 (1963) 1858–1862.[30] R.A. Marcus, J. Chem. Phys. 38 (1963) 1335–1340.

Fig. 6. Plot of log (knr/kr) vs. ET(30) of different solvents for A.

onded probe molecules are dissipating energy via non-radiativeathways. The substitution of –OCH3 group in B and C decreaseshe ratio of knr and kr. The effect is greater in C due to the presencef two –OCH3 groups. The order of decreasing log (knr/kr) in differ-nt solvents is A > B > C as observed from the slope values of the plotf log (knr/kr) vs. ET(30). The hydrogen bond forming ability of theompounds decreases in the order A > B > C. For DMF, the points areelow the line since the compounds have higher lifetime value inMF due to electron transfer process.

. Conclusions

The photophysical properties of the thiazolidinedione deriva-ives are governed mainly by three factors: (1) polarity of the

edium and (2) hydrogen bonding and (3) substitution effect.he aryl substituents play a major role in the hydrogen bondormation ability of the three probes. The absorbance and the flu-rescence spectra clearly depict the solvent polarity dependencef the probes, whereas the diminished fluorescence intensities ofhe probes in polar solvents indicate the formation of a hydrogenond resulting in radiationless decay. In glycerol and ethylene gly-ol, the probes exhibit enhanced fluorescence intensities due tohe viscosity of the medium. The probes behave differently withCN and DMF. The compounds have a potential electron deficiententer at –NH and electron rich centers at the carbonyl oxygen.

ith ACN, there exists a dipolar interaction of the probes, whereasith electron donating solvent DMF, an electron transfer processrobably occurs from the electron rich DMF to the electron defi-

ient –NH center for all the probes. The extent of transfer is againependent on the aryl substituents, as they affect the electron den-ity on the –NH group. The high non-radiative rate constants andhe short lifetime values of the probes in polar solvents reveal theossibility of a radiationless decay via hydrogen bonding. In DMF

[[[

Part A 72 (2009) 1097–1102

the values are reversed due to a completely different interaction.The photophysical study of these newly synthesized and biologi-cally important thiazolidinedione derivatives help in assessing theirpotential application in different homogeneous environments.

Acknowledgement

One of the authors A.S. thanks UGC for providing a SRF.

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